Yohan Rigaldie

The stenlying effect of high hydrostatic pressure on thermally and hydrolytically labile nanosized carriers.

AbstractPurpose. To investigate whether high hydrostatic pressure (HHP) treatment allows the sterilization of thermosensitive polymer nanoparticle suspensions without jeopardizing their physicochemical integrity. Methods. Application of HHP was explored on a wide variety of thermosensitive poly(cyanoacrylate) nanoparticles, varying by their type (nanospheres or nanocapsules), by their preparation method (nanoprecipitation or emulsion/solvent evaporation), as well as by their surface characteristics. Physicochemical characterization before and after pressurization included turbidimetry, size measurement, zeta potential, scanning electron microscopy and infrared analysis. A sterility test also conducted according to pharmacopoeial requirements on an importantly contaminated nanoparticle suspension. Results. Poly(cyanoacrylate) nanoparticles appeared to be extremely baroresistant. Continuous or oscillatory HHP treatment up to 500 MPa during 30 min induced generally neither physical, nor chemical damage. However, precautions should be taken when surface modifiers are adsorbed onto nanoparticles, as a layer destabilization may occur. Finally, this process allowed the successful inactivation of vegetative bacteria, yeast, and fungi. Conclusions. This work proposes HHP as a new method for polymer drug carriers sterilization, taking into account that further exploration in this area is needed to propose novel protocols for spores inactivation.

Effects of High Hydrostatic Pressure on Several Sensitive Therapeutic Molecules and a Soft Nanodispersed Drug Delivery System

AbstractPurpose. According to the development in the last decade of industrial processes using high hydrostatic pressure (HHP) for preservation of several commercial food products, novel sterilization or decontamination processes for pharmaceutical products could be conceivable. The aim of this work is to evaluate the effects of HHP on the integrity of insulin and heparin solutions, suspension of monoclonal antibodies and Spherulites®. Methods. High performance liquid chromatography, thin layer chromatography, capillary electrophoresis assays, ELISA tests, laser granulometry and spectrophotometry analyses have been performed to compare HHP treated drugs (in a domain of pressure and temperature ranging respectively from 20 up to 500 MPa and from 20°C up to 37°C) vs. untreated ones. Results. No difference has been detected except for monoclonal antibodies that are altered above 500 MPa. Conclusions. The structure integrity of sensitive molecule due to the small energy involved by HHP and the development of industrial plants (intended for the decontamination of food products) confer to this technology the potential of a new method for sterilization of fragile drugs and an original alternative to aseptic processes and sterilizing filtration.

Inactivation of Staphylococcus aureus using high hydrostatic pressure

The aim of this work was to develop a high-pressure decontamination and sterilization process for pharmaceutical treatments as was developed in food processing in the late eighties. The lack of normalized biological indicators able to validate sterilizing treatments under high pressure led us to select representative pathogenic strains from flora and the European Pharmacopoeia. We selected the following four bacterial strains: Candida albicans (ATCC 10231), Psuedomonas aeruginosa (ATCC 9027), spores of Aspergillus niger (ATCC 16404) and Staphylococcus aureus (ATCC 6538). This present study is focussed on S. aureus. Successive pressurization and depressurization cycles appeared to be more efficient than a continuous high-pressure treatment. Importantly, these pressure conditions, temperature and process duration are perfectly compatible with current industrial plants. These results show that HHP technology is a new alternative to inactivate pathogenic strains in accordance with pharmaceutical requirements.

Sterilization of Liquid and Semi-Solid Pharmaceutical Forms Using High Pressure Technology

The aim of this study was to investigate the use of HHP (High Hydrostatic Pressure) technology as a possible alternative method for decontamination and sterilization of sensitive drugs. We demonstrated the safety of HHP treatment on several sensitive biomolecules. A 10 min. HHP treatment inactivates totally pure suspensions of P. aeruginosa , C. albicans and spores of A. niger , but S. aureus needs a longer HHP duration treatment to be totally inactivated. Endospores appear to be more baroresistant.